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Genetic cardiovascular diseases influence pulmonary inflammatory responses to oxidant pollutants - insights from transcription profiling
Citation:
KODAVANTI, U. P., W. O. WARD, M. SCHLADWEILER, AND A. D. LEDBETTER. Genetic cardiovascular diseases influence pulmonary inflammatory responses to oxidant pollutants - insights from transcription profiling. Presented at Aspen Lung Conference, Aspen, CO, June 09 - 13, 2009.
Impact/Purpose:
This abstract compared susceptibility of 5 rate models of cardiovascular diseases to ozone and showed that baseline differences in gene expression pattern and underlying pathology influence ozone-induced toxicity to the lung.
Description:
Metals are ubiquitously present in ambient PM especially in the vicinity of coal and oilfired power plants, smelters and roads. The presence of neighboring emission sources influences ambient levels of metals. Because inhaled PM-associated metals can be labile, their translocation to extrapulmonary organs can influence systemic toxicity. Although several studies in the past have demonstrated translocation of metals, we systematically evaluated whether PM-associated metals translocate and how solubility affects their kinetics of translocation. We first reported that non-essential metals such as nickel and vanadium translocated rapidly when PM containing these metals was instilled in rat lungs. Translocation was detected in the extrapulmonary organs including heart, liver and kidney. Although it was possible to demonstrate translocation of non-essential metals, we could not confirm that such may be happening with essential metals because of high endogenous levels. Using a stable zinc isotope (QZn) with low natural abundance (0.6%), we recently studied the kinetics of zinc translocation, and demonstrated that cardiac tissue is exposed at a much higher concentration after pulmonary exposure than oral gavage, and that systemic essential metal homeostasis is disturbed. The translocation kinetics was affected by the solubility and the type of metal present in PM. Tightly bound metals that leach only in acidic solution, also translocated systemically after long-term exposure in rats, suggesting that these metals can have long lasting pulmonary and extrapulmonary effects. Thus, our studies provide evidence that PM-associated metals can have implications in extrapulmonary health outcomes following inhalation of metal-rich PM. (Does not reflect US EPA policy).